The present invention is related to a method of using 7-(substituted)amino-8-((substituted)carbonyl)methylamino)-1-oxaspiro(4.5) decanes or pharmaceutically acceptable salts thereof as agents for treating benign prostatic hyperplasia. Enadoline, chemical name, (-)-5.alpha.,7.alpha.,-8.alpha.-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[ 4.5]dec-8-yl]-4-benzofuranacetamide monohydrochloride, with the chemical structure ##STR1## is especially effective. Enadoline, also known as CI-977, is a kappa-opioid agonist with analgesic properties which also causes sedation, diuresis, and elevation of corticosteroids.
U.S. Pat. No. 5,317,028 is related to a method of using 7-(substituted)amino-8-((substituted)-carbonyl)-methylamino-1-oxaspiro(4.5 )decanes and the pharmaceutically acceptable salts thereof as agents useful in treating Parkinson's disease, dystonia, and other movement disorders. The compounds, processed for preparing them, and pharmaceutical compositions containing them are found in U.S. Pat. No. 4,737,493, which is herein incorporated by reference. The disclosed utility in the patent is analgesic. The compounds are also disclosed as having sedative, diuretic, and corticosteroid elevating effects and therefore as being useful diuretic and psychotherapeutic agents.
U.S. Pat. No. 4,965,278 and its divisional U.S. Pat. No. 5,063,242 cover use of the above compounds for inflammation, stroke, and cerebrovascular disorders such as cerebral ischemia and infarction. These two patents are hereby incorporated by reference.
U.S. Pat. No. 5,369,120 relates to a pharmaceutical composition having synergistic effects using the above compounds and L-Dopa.
Benign enlargement of the prostate (nodular hyperplasia, benign prostatic hyperplasia/hypertrophy, BPH) is a common age-associated condition in humans. By age 60, it is estimated that 70% of men have prostatic nodular hyperplasia and that 50% of these men have symptoms related to prostatic enlargement. In both dogs and humans, development of prostatic enlargement is dependent on androgen exposure and dihydrotestosterone (DHT) is considered to be the principal mediator of prostatic hyperplasia. There appears to be an age-related propensity for DHT to accumulate in the prostate which may in part explain the high incidence of prostatic hyperplasia in the elderly. Symptoms associated with prostatic enlargement are considered secondary to either compression of the urethra with impairment of urination or retention of urine within the urinary bladder resulting in predisposition for development of urinary tract infection (S. L. Robins, et al, Pathologic Basis Of Disease 1994;5:1025-6).
The predominant treatment for symptomatic benign prostatic enlargement is transurethral prostatic resection. In fact, in males over 65 years of age, it is estimated that prostatic resection is second only to cataract extraction in number of surgical procedures performed each year. Due to the morbidity and expense associated with surgery, effective medical therapies are preferred.
Currently, there are two medical therapies for BPH: 5.alpha.-reductase inhibitors and .alpha.-adrenergic antagonists. Inhibition of 5.alpha.-reductase blocks the conversion of testosterone to DHT, thereby reducing androgenic stimulation for prostatic hyperplasia. Although 5.alpha.-reductase inhibitors, specifically finasteride, are well-tolerated, prolonged treatment (6-12 months) may be required to elicit beneficial effects (D. H. Peters, et al, Drugs 1993;46:177-208). The .alpha.-adrenergic antagonists provide symptomatic relief by reducing muscle tone in the urinary bladder and prostate, thereby decreasing resistance to urinary flow in the prostatic urethra (J. M. Monda, et al, Mayo Clinic Proc 1993;68:670-9). While both of these therapeutic approaches are useful, additional medical therapies which treat the underlying hyperplastic process and provide symptomatic relief within a shortened timeframe, will be valuable in treatment of BPH.